October 06, 2015 – Lung cancer is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. Among lung cancers, non-small cell lung cancer (NSCLC) is the most common type of lung cancer.
Very recently, the American Food and Drug Administration (FDA) granted accelerated approval for Prembrolizumab (Keytruda) to treat patients with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1 which is encoded by the CD274 gene in humans. In this case, Prembolizumab (Keytruda) was approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.
This is remarkable in two ways. On one hand, in 2014, Prembolizumab (Keytruda) was already approved to treat patients with advanced melanoma following treatment with ipilimumab, a type of immunotherapy. With the present approval of Prembolizumab (Keytruda) it seems that one molecular target, PD-L1 in this case, may play a role in different types of cancers, and therefore make one single drug useful in the therapy of a number of cancer-related indications. On the other hand, Prembolizumab (Keytruda) was approved for treatment of NSCLC to be used together with the the PD-L1 IHC 22C3 pharmDx test: In other words, physicians are able to target their therapy towards patients whose tumors express PD-L1 and are therefore particularly amenable to the therapeutic effects of Prembolizumab (Keytruda).
Prembolizumab (Keytruda) works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Prembolizumab (Keytruda) may help the body’s immune system fight the cancer cells. Another drug, Nivolumab (Opdivo), also targets the PD-1/PD-L1 pathway and was approved to treat squamous non-small cell lung cancer (a certain kind of NSCLC) in 2015.
The effectiveness of Prembolizumab (Keytruda) in NSCLC was demonstrated in a subgroup of 61 patients enrolled within a larger multicenter, open-label, multi-part study. The subgroup consisted of patients with advanced NSCLC that progressed following platinum-based chemotherapy or, if appropriate, targeted therapy for certain genetic mutations (ALK or EGFR). This subgroup also had PD-L1 positive tumors based on the results of the 22C3 pharmDx diagnostic test. Study participants received 10 mg/kg of Keytruda every two or three weeks. The major outcome measure was overall response rate (percentage of patients who experienced complete and partial shrinkage of their tumors). Tumors shrank in 41 percent of patients treated with Keytruda and the effect lasted between 2.1 and 9.1 months.
The flip-side of the coin is that Prembolizumab (Keytruda) comes with a rather complicated and serious profile of adverse effects. Thus, according to FDA, the safety of Prembolizumab (Keytruda) was studied in 550 patients with advanced NSCLC. The most common side effects of Prembolizumab (Keytruda) included fatigue, decreased appetite, shortness of breath or impaired breathing (dyspnea) and cough. However, Prembolizumab (Keytruda) also has the potential to cause severe side effects that result from the immune system effect of Prembolizumab (Keytruda) (known as “immune-mediated side effects”). In the 550 study participants with advanced NSCLC, severe immune-mediated side effects occurred involving the lungs, colon and hormone-producing glands. Other uncommon immune-mediated side effects were rash and inflammation of blood vessels (vasculitis). Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby. Across clinical studies, a disorder in which the body’s immune system attacks part of the peripheral nervous system (Guillain-Barre Syndrome) also occurred.